Biomedical subjects

Jacob V Maizel

Publications and source records attributed to Jacob V Maizel.

4 recordsLinked to original sources

PubMed2004

An algorithm for detecting homologues of known structured RNAs in genomes.

Distinct RNA structures are frequently involved in a wide-range of functions in various biological mechanisms. The three dimensional RNA structures solved by X-ray crystallography and various well-established RNA phylogenetic structures indicate that functional RNAs have characteristic RNA structural motifs represented by specific combinations of base pairings and conserved nucleotides in the loop region. Discovery of well-ordered RNA structures and their homologues in genome-wide searches will enhance our ability to detect the RNA structural motifs and help us to highlight their association with functional and regulatory RNA elements. We present here a novel computer algorithm, HomoStRscan, that takes a single RNA sequence with its secondary structure to search for homologous-RNAs in complete genomes. This novel algorithm completely differs from other currently used search algorithms of homologous structures or structural motifs. For an arbitrary segment (or window) given in the target sequence, that has similar size to the query sequence, HomoStRscan finds the most similar structure to the input query structure and computes the maximal similarity score (MSS) between the two structures. The homologousRNA structures are then statistically inferred from the MSS distribution computed in the target genome. The method provides a flexible, robust and fine search tool for any homologous structural RNAs.

Algorithms↗

PubMed2003

Discovering well-ordered folding patterns in nucleotide sequences.

MOTIVATION: Growing evidence demonstrates that local well-ordered structures are closely correlated with cis-acting elements in the post-transcriptional regulation of gene expression. The prediction of a well-ordered folding sequence (WFS) in genomic sequences is very helpful in the determination of local RNA elements with structure-dependent functions in mRNAs. RESULTS: In this study, the quality of local WFS is assessed by the energy difference (E(diff)) between the free energies of the global minimal structure folded in the segment and its corresponding optimal restrained structure (ORS). The ORS is an optimal structure under the condition in which none of the base-pairs in the global minimal structure is allowed to form. Those WFSs in HIV-1 mRNA, various ferritin mRNAs and genomic sequences containing let-7 RNA gene were searched by a novel method, ed_scan. Our results indicate that the detected WFSs are coincident with known Rev response element in HIV-1 mRNA, iron-responsive elements in ferritin mRNAs and small let-7 RNAs in Caenorhabditis elegans, Caenorhabditis briggsae and Drosophila melanogaster genomic sequences. Statistical significance of the WFS is addressed by a quantitative measure Zscr(e) that is a z-score of E(diff) and extensive random simulations. We suggest that WFSs with high statistical significance have structural roles involving their sequence information. AVAILABILITY: The source code of ed_scan is available via anonymous ftp as ftp://ftp.ncifcrf.gov/pub/users/shuyun/scan/ed_scan.tar.

Algorithms↗

PubMed2002

RNA molecules with structure dependent functions are uniquely folded.

Cis-acting elements in post-transcriptional regulation of gene expression are often correlated with distinct local RNA secondary structure. These structures are expected to be significantly more ordered than those anticipated at random because of evolutionary constraints and intrinsic structural properties. In this study, we introduce a computing method to calculate two quantitative measures, NRd and Stscr, for estimating the uniqueness of an RNA secondary structure. NRd is a normalized score based on evaluating how different a natural RNA structure is from those predicted for its randomly shuffled variants. The lower the score NRd the more well ordered is the natural RNA structure. The statistical significance of NRd compared with that computed from structural comparisons among large numbers of randomly permuted sequences is represented by a standardized score, STSCR: We tested the method on the trans-activation response element and Rev response element of HIV-1 mRNA, internal ribosome entry sequence of hepatitis C virus, Tetrahymena thermophila rRNA intron, 100 tRNAs and 14 RNase P RNAs. Our data indicate that functional RNA structures have high Stscr, while other structures have low Stscr. We conclude that RNA functional molecules and/or cis-acting elements with structure dependent functions possess well ordered conformations and they are uniquely folded as measured by this technique.

Animals↗

PubMed2002

The hydrophobic effect: a new insight from cold denaturation and a two-state water structure.

Herein we provide a new insight into the hydrophobic effect in protein folding. Our proposition explains the molecular basis of cold denaturation, and of intermediate states in heat and their absence in cold denaturation. The exposure of non-polar surface reduces the entropy and enthalpy of the system, at low and at high temperatures. At low temperatures the favorable reduction in enthalpy overcomes the unfavorable reduction in entropy, leading to cold denaturation. At high temperatures, folding/unfolding is a two-step process: in the first, the entropy gain leads to hydrophobic collapse, in the second, the reduction in enthalpy due to protein-protein interactions leads to the native state. The different entropy and enthalpy contributions to the Gibbs energy change at each step at high, and at low, temperatures can be conveniently explained by a two-state model of the water structure. The model provides a clear view of the dominant factors in protein folding and stability. Consequently, it appears to provide a microscopic view of the hydrophobic effect and is consistently linked to macroscopic thermodynamic parameters.

Cold Temperature↗